• Blood will be taken for genotyping of CYP2C19 at study day 1.
• HIV-1 RNA and CD4 determination will be done (HIV patients only) at inclusion screening

Malarone® (atovaquone/proguanil) is frequently used in malaria prophylaxis. Unfortunately, there are indications that certain anti-HIV agents may decrease atovaquone plasma levels by induction of atovaquone metabolism.

For travelling HIV patients, the clinical consequences of these possible drug drug interactions are serious, since a diminished exposure to the anti-malarial drug will result in suboptimal prophylaxis of malaria and potential development of drug resistant strains of Plasmodium falciparum.

The purpose of this study is to find out if HIV patients using HAART regimes with either lopinavir/ritonavir, atazanavir/ritonavir or efavirenz have lower atovaquone plasma levels than healthy volunteers after a single dose of atovaquone/proguanil.

• HIV Infections
• Malaria

Inclusion Criteria:

For healthy volunteers

• 18 - 65 years
• smoking habits < 10 cigarettes, 2 cigars or 2 pipes
• BMI between 18 and 30 kg/m2
• able and willing to sign informed consent form
• subject is in a good age-appropriate health condition
• subject has a normal blood pressure and pulse rate

For HIV patients

• HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
• CD4+ > 200 * 10E6 per Liter.
• 18 - 65 years
• BMI between 18 and 30 kg/m2
• able and willing to sign informed consent form
• use of lopinavir/ritonavir, atazanavir/ritonavir or efavirenz for at least 1 month in a dose of 400/100mg bid, 300/100 mg QD, or 600 mg QD respectively

Exclusion Criteria healthy volunteers:

• History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients.
• Positive HIV test.
• Positive HbsAg test (hepatitis B) or positive hepatitis C test.
• Therapy with any drug (for two weeks preceding dosing), except for paracetamol.
• Creatinine clearance < 60 mL/min (calculated from serum creatinine)
• Current diarrhoea.
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
• History of or current abuse of drugs, alcohol or solvents.
• Inability to understand the nature and extent of the trial and the procedures required.
• Participation in a drug trial within 60 days prior to the first dose.
• Donation of blood within 60 days prior to the first dose.
• Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female.
• Abnormal serum transaminases, determined as levels being > 3 times up-per limit of normal
• Febrile illness within 3 days before the first dose

Exclusion criteria HIV patients:

• History of sensitivity/idiosyncrasy to atovaquone/proguanil or chemically related compounds or excipients.
• Suspicion of non-adherence to the HIV medication.
• Current diarrhoea.
• Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
• Inability to understand the nature and extent of the trial and the procedures required.
• Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female.
• Abnormal serum transaminases determined as levels being > 3 times upper limit of normal
• Creatinine clearance < 60 mL/min (calculated from serum creatinine).
• Any change in antiretroviral medication within 1 month immediately pre- ceding the dose of atovaquone/proguanil.
• Concomitant use of medications that interfere with atovaquone or proguanil pharmacokinetics: anti-coagulants, aurothioglucose, chloroquine, cimetidine, fluoxetine, fluvoxamine, metoclopramide, omeprazole, magnesiumtrisilicate, rifabutin, rifampin, tetracycline, typhoid vaccine, topiramate.
• Use of a HAART regime containing both lopinavir/ritonavir and another protease inhibitor or a NNRTI.
• Use of a HAART regime containing both atazanavir/ritonavir and another protease inhibitor or a NNRTI.
• Use of a HAART regime containing both efavirenz and one or more protease inhibitors or nevirapine.
• Active hepatobiliary or hepatic disease
• Alcohol abuse